Low versus high level of response to alcohol affects amygdala functional connectivity during processing of emotional stimuli.

BACKGROUND: Low levels of response (low LR) to alcohol predict heavy drinking and alcohol problems. Functional magnetic resonance imaging (fMRI) studies of emotion processing have shown that low LR individuals exhibit lower activation in task-related brain regions following both placebo and alcohol administration, but these studies did not examine functional brain networks that might contribute to the phenomena. The current study expands upon the earlier results by evaluating whether functional connectivity differences between the amygdala and other brain regions modulated by emotional face processing are associated with LR. Based on prior findings, we hypothesized that low LR is related to lower functional connectivity in fronto-amygdalar functional circuits, which underlie the processing of emotional stimuli. METHODS: Secondary analyses were conducted on data from a double-blind, placebo-controlled, within-subjects, cross-over study in 108 18-to-25-year-old low and high LR sex-matched pairs without alcohol use disorder at baseline. Participants performed modified emotional faces processing tasks after receiving placebo or approximately 0.7 ml/kg of ethanol. Psychophysiological interaction analyses examined functional connectivity between left and right amygdalae and related brain circuits using LR-by-alcohol general linear models. The data included 54 sex-matched pairs with 216 fMRI scans comprising alcohol and placebo conditions. RESULTS: Compared with individuals with high LR, low LR subjects demonstrated lower functional connectivity between the amygdala and the frontal lobes, insula, and parietal regions, while processing angry and happy faces. Interactions showed lower connectivity following alcohol in low LR and higher connectivity in high LR groups. CONCLUSIONS: Low LR individuals demonstrated lower functional connectivity in response both to placebo and a modest dose of ethanol. Attenuated connectivity among low LR individuals when processing emotional faces may contribute to an impaired ability to recognize alcohol intoxication in social situations and to appraise angry and happy emotions irrespective of whether alcohol is consumed.

Relationship between level of response to alcohol and acute tolerance.

BACKGROUND: A low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session. METHODS: Data were generated through a reanalysis of data from 120 individuals who were 18- to 25-year-old, sex-matched pairs of low and high LR drinkers who at baseline did not meet criteria for an alcohol use disorder. Each subject participated in an oral alcohol challenge in which they consumed about 0.7 ml ethanol per kg and acute tolerance was measured as the differences in alcohol's effects at similar breath alcohol levels (BrACs) during the rising and falling breath alcohol concentration (BrAC) curve. Measures included aspects of the Subjective High Assessment Scale (SHAS) and body sway. RESULTS: Contrary to our hypothesis, but similar to results with other alcohol measures, acute tolerance was significantly attenuated in low LR compared with high LR individuals on most SHAS scores. Neither LR group demonstrated acute tolerance to alcohol for sleepiness or body sway. Men and women did not differ on any of these measures. CONCLUSION: These data do not support a role of acute tolerance in the low LR to alcohol as measured by subjective feelings of intoxication or body sway in these subjects, findings that were similar across males and females. In addition, consistent with the literature, the analyses demonstrated differences across measures such that acute tolerance was observed for most measures of subjective effects but not for body sway. Among the subjective effects, acute tolerance was observed for alcohol's intoxicating effect but not for feeling sleepy.

Ethanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release.

Norepinephrine adjusts sensory processing in cortical networks and gates plasticity enabling adaptive behavior. The actions of norepinephrine are profoundly altered by recreational drugs like ethanol, but the consequences of these changes on distinct targets such as astrocytes, which exhibit norepinephrine-dependent Ca2+ elevations during vigilance, are not well understood. Using in vivo two-photon imaging, we show that locomotion-induced Ca2+ elevations in mouse astroglia are profoundly inhibited by ethanol, an effect that can be reversed by enhancing norepinephrine release. Vigilance-dependent astroglial activation is abolished by deletion of α1A-adrenergic receptor from astroglia, indicating that norepinephrine acts directly on these ubiquitous glial cells. Ethanol reduces vigilance-dependent Ca2+ transients in noradrenergic terminals, but has little effect on astroglial responsiveness to norepinephrine, suggesting that ethanol suppresses their activation by inhibiting norepinephrine release. Since abolition of astroglia Ca2+ activation does not affect motor coordination, global suppression of astroglial networks may contribute to the cognitive effects of alcohol intoxication.

Analysis of BMSCs-intervened viscoelasticity of sciatic nerve in rats with chronic alcoholic intoxication 1.

PURPOSE: To investigate the impact of bone mesenchymal stem cells (BMSCs) intervention on the viscoelasticity of sciatic nerve in rats with chronic alcohol intoxication (CAI). METHODS: The CAI rat models were prepared, divided into model groups, and treated with either BMSCs or basic fibroblast growth factor (bFGF). Then the rats underwent electrophysiological test and the serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and metallothionein (MT) were measured. Histological observation, stress relaxation test, and creep test were performed for the sciatic nerve of the CAI model in each group. RESULTS: The MDA level of group BMSC was significantly lower (p<0.05) than that of groups MOD (the CIA model) and bFGF. The SOD and MT levels were higher in group BMSC than in groups MOD and bFGF (p<0.05). The motor nerve conduction velocity and amplitude were higher in group BMSC than in groups MOD and bFGF (p<0.05). The amounts of 7200s stress reduction and 7200 s strain increase of the sciatic nerve in group BMSC were greater than those in groups bFGF and MOD (p<0.05). CONCLUSION: Bone mesenchymal stem cells can improve the metabolism of free radicals, restore the tissue morphology and viscoelasticity of the chronic alcohol intoxication animal model, and positively affect the repairing of the injured sciatic nerve.

Analysis of BMSCs-intervened viscoelasticity of sciatic nerve in rats with chronic alcoholic intoxication

Abstract Purpose: To investigate the impact of bone mesenchymal stem cells (BMSCs) intervention on the viscoelasticity of sciatic nerve in rats with chronic alcohol intoxication (CAI). Methods: The CAI rat models were prepared, divided into model groups, and treated with either BMSCs or basic fibroblast growth factor (bFGF). Then the rats underwent electrophysiological test and the serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and metallothionein (MT) were measured. Histological observation, stress relaxation test, and creep test were performed for the sciatic nerve of the CAI model in each group. Results: The MDA level of group BMSC was significantly lower (p<0.05) than that of groups MOD (the CIA model) and bFGF. The SOD and MT levels were higher in group BMSC than in groups MOD and bFGF (p<0.05). The motor nerve conduction velocity and amplitude were higher in group BMSC than in groups MOD and bFGF (p<0.05). The amounts of 7200s stress reduction and 7200 s strain increase of the sciatic nerve in group BMSC were greater than those in groups bFGF and MOD (p<0.05). Conclusion: Bone mesenchymal stem cells can improve the metabolism of free radicals, restore the tissue morphology and viscoelasticity of the chronic alcohol intoxication animal model, and positively affect the repairing of the injured sciatic nerve.

Effects of acute ethanol intoxication in an ovine peritonitis model.

BACKGROUND: Acute ethanol intoxication has been shown to have contrasting effects on outcomes in sepsis. The aim of this study was to explore the effects of acute ethanol intoxication on hemodynamics, renal function, brain perfusion and lactate/pyruvate in an ovine sepsis model. METHODS: Anesthetized, mechanically ventilated female sheep were randomized to an ethanol group (n = 7), which received 1 g/kg ethanol diluted in intravenous (i.v.) saline infusion or a control group (n = 7), which received the same volume of i.v. saline. Both groups received the treatment for a period of 2 h prior to induction of sepsis by intraperitoneal injection of feces. Other treatment included fluid resuscitation but no vasopressors or antibiotics. Global hemodynamics, renal blood flow, brain cortex laser Doppler flowmetry and microdialysis analyses were recorded hourly. RESULTS: In the ethanol group, blood ethanol concentrations were 137 ± 29 mg/dL at the time of feces injection and decreased to become undetectable by 12 h. Arterial hypotension occurred earlier in the ethanol than in the control group (8 [7-12] vs. 14 [11-20] hours, p = 0.03). Lactate levels increased to > 2 mmol/L earlier in the ethanol group. Renal dysfunction (9 [6-13] vs. 13 [12-15] hours, p = 0.05) and oliguria (urine output < 0.5 mL/kg/h; 10 [7-12] vs. 13 [12, 13] hours, p = 0.01) developed earlier in the ethanol than in the control group. Brain blood flow and lactate/pyruvate were unaffected. There was no significant difference in survival time. CONCLUSIONS: Acute ethanol intoxication in this model of peritonitis resulted in earlier development of shock and renal dysfunction but did not alter brain perfusion and metabolism or short-term survival.

Acute alcohol effects on set-shifting and its moderation by baseline individual differences: a latent variable analysis.

AIMS: To compare the acute effects of alcohol on set-shifting task performance (relative to sober baseline performance) during ascending and descending limb breath alcohol concentration (BrAC), as well as possible moderation of these effects by baseline individual differences. DESIGN: Shifting performance was tested during an initial baseline and a subsequent drinking session, during which participants were assigned randomly to one of three beverage conditions (alcohol, placebo or control) and one of two BrAC limb conditions [ascending and descending (A/D) or descending-only (D-only)]. SETTING: A human experimental laboratory on the University of Missouri campus in Columbia, MO, USA. PARTICIPANTS: A total of 222 moderate-drinking adults (ages 21-30 years) recruited from Columbia, MO and tested between 2010 and 2013. MEASUREMENTS: The outcome measure was performance on set-shifting tasks under the different beverage and limb conditions. Shifting performance assessed at baseline was a key moderator. FINDINGS: Although performance improved across sessions, this improvement was reduced in the alcohol compared with no-alcohol groups (post-drink latent mean comparison across groups, all Ps ≤ 0.05), and this effect was more pronounced in individuals with lower pre-drink performance (comparison of pre- to post-drink path coefficients across groups, all Ps ≤ 0.05). In the alcohol group, performance was better on descending compared with ascending limb (P ≤ 0.001), but descending limb performance did not differ across the A/D and D-only groups. CONCLUSIONS: Practising tasks before drinking moderates the acute effects of alcohol on the ability to switch between tasks. Greater impairment in shifting ability on descending compared with ascending breath alcohol concentration is not related to task practice.

Acute alcohol intoxication and bispectral index monitoring.

BACKGROUND: Bispectral index (BIS) monitoring is commonly used to decrease the risk of awareness during anaesthesia. We aimed to determine the relationship between blood alcohol concentration and brain function (as measured by BIS) in healthy adults. METHODS: In this prospective observational study, 21 anaesthetic registrars self-regulated alcohol consumption over a 3-h period. Expired alcohol concentration (breathalyser) and BIS measurements were performed hourly for 4 h. A venous blood alcohol sample was taken at the conclusion of the study period. RESULTS: The main outcome measures were the correlation between blood alcohol and brain function as measured by BIS and the change in BIS from baseline (∆BIS) at 4 h. The median number of standard drinks consumed was 9.1 (IQR 7.7-12.3), range 5.4-17. At 4 h, there was a moderate inverse correlation between BIS and blood alcohol (r = -0.49, P = 0.029) and between ∆BIS and blood alcohol (r = -0.46, P =0.043). CONCLUSION: In healthy young adults, we found a moderate correlation between venous blood alcohol concentration and BIS. This suggests that acute alcohol consumption can decrease BIS. This information may be relevant when providing anaesthesia to intoxicated patients who require urgent or time-critical surgery, although certain limitations of this study should be kept in mind.

Alcohol and tobacco cue effects on craving in non-daily smokers.

Non-daily smokers commonly smoke cigarettes following the consumption of alcohol, yet the reason(s) for this remains poorly understood. The present study examined the impact of alcohol consumption on responses in tobacco salient cues 49 male and 50 female non-daily smokers. After the administration of an alcohol, placebo, or control beverage, participants were exposed to series neutral video clips and tobacco smoking salient video clips, and their subjective states and heart rates were monitored. The timing of the exposure to the tobacco smoking clips was randomly determined to coincide with the timing of either the ascending limb or the descending limb of the blood alcohol concentration (BAC) curve of the alcohol beverage condition. The tobacco smoking clips were found to increase cigarette craving regardless of beverage condition or timing of exposure (p = .002). Alcohol consumption was associated with increased ratings of intoxication (p < .001), increased heart rate across participants (p < .001), and increased cigarette craving in female participants specifically (p = .017). Alcohol did not influence responses to the smoking videos. These results suggest that smoking salient cues and alcohol may impact cigarette craving in non-daily smokers through independent processes.

Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.

Does the severity of hangovers decline with age? Survey of the incidence of hangover in different age groups.

BACKGROUND: Alcohol hangover is a growing research area, but differences across the life span have not been assessed. Here, we test the hypothesis that the severity of hangovers depends on age. METHODS: A cross-sectional study of 51,645 men and women aged 18 to 94 years old, who participated in the population-based Danish Health Examination Study (DANHES) in Denmark between 2007 and 2008, formed the database for our study. RESULTS: The incidence of severe hangover was lower among older than younger participants. Odds ratios for experiencing severe hangover following an episode of binge drinking were 6.8, 4.8, 3.0, and 2.0 among the 18 to 29, 30 to 39, 40 to 49, and 50 to 59-year-old men, compared with those aged 60+ years. For women, similar results were obtained. This finding could not be explained by the usual amount of alcohol consumption, frequency of binge drinking, or the proportion of alcohol consumed with meals. CONCLUSIONS: We found that hangover following engagement in binge drinking is much more common in the young than in the older age groups.

Does acute alcohol intoxication interfere with colonic anastomosis wound healing?: a rat model of nondestructive colon trauma

PURPOSE: To evaluate the effects of acute alcohol intoxication on healing of colonic anastomosis. METHODS: Thirty-six rats were allocated into two groups. Animals in the alcohol (A) were given 2 mL of ethanol diluted in 0.9% saline solution to a concentration of 40% by gavage immediately before anesthesia, whereas control (C) animals received 2 mL of 0.9% saline solution via the same route. A colonic anastomosis was then performed in all animals. On postoperative days 1, 3, and 7, anastomotic breaking strength was assessed and histopathological examination was performed. Change in body weight and mortality were also evaluated. RESULTS: The median of anastomotic tensile strength on the postoperative day 1 was 0.09 Newtons for group A and 0.13 for group C. (p>0.05). The median of anastomotic tensile strength on the postoperative day 3 was 0.13 Newtons for group A and 0.17 for group C. (p>0.05). The median of anastomotic tensile strength on the postoperative day 7 was 0.30 Newtons for group A and 0.35 for group C. (p>0.05). There was no significant difference between the groups A and C, in the first, third or seventh POD (p>0.05), in any of the analyzed parameters. There were no statistical differences between groups in the weight. Three animals died, all from the group A. CONCLUSION: Acute alcohol intoxication did not interfere with wound healing of colonic anastomoses, although it caused early postoperative mortality.

Hypertonic saline resuscitation enhances blood pressure recovery and decreases organ injury following hemorrhage in acute alcohol intoxicated rodents.

BACKGROUND: Acute alcohol intoxication (AAI) impairs the hemodynamic and arginine vasopressin (AVP) counter-regulation to hemorrhagic shock (HS) and lactated Ringer's solution (LR) fluid resuscitation (FR). The mechanism of AAI-induced suppression of AVP release in response to HS involves accentuated nitric oxide (NO) inhibitory tone. In contrast, AAI does not prevent AVP response to increased osmolarity produced by hypertonic saline (HTS) infusion. We hypothesized that FR with HTS during AAI would enhance AVP release by decreasing periventricular nucleus NO inhibitory tone, subsequently improving mean arterial blood pressure (MABP) and organ perfusion. METHODS: Male Sprague-Dawley rats received a 15-hour alcohol infusion (2.5 g/kg + 0.3 g/kg/h) or dextrose (DEX) before HS (40 mm Hg × 60 minutes) and FR with HTS (7.5%, 4 ml/kg) or LR (2.4 × blood volume removed). Organ blood flow was determined, and brains were collected for NO content at 2 hours after FR. RESULTS: HTS improved MABP recovery in AAI (109 vs. 80 mm Hg) and DEX (114 vs. 83 mm Hg) animals compared with LR. This was associated with higher (>60%) circulating AVP levels at 2 hours after FR compared with those detected in LR animals in both groups. Neither AAI alone nor HS in DEX animals resuscitated with LR altered organ blood flow. In AAI animals, HS and FR with LR reduced blood flow to the liver (72%), small intestine (65%), and large intestine (67%) compared with shams. FR with HTS improved liver (threefold) and small intestine (twofold) blood flow compared with LR in AAI-HS animals. The enhanced MABP response to HTS was prevented by pretreatment with a systemic AVP V1a receptor antagonist. HTS decreased periventricular nucleus NO content in both groups 2 hours after FR. CONCLUSION: These results suggest that FR with HTS in AAI results in the removal of central NO inhibition of AVP, restoring AVP levels and improving MABP and organ perfusion in AAI-HS.

Protective effect of blackcurrant on liver cell membrane of rats intoxicated with ethanol.

Chronic ethanol intoxication oxidative stress participates in the development of many diseases. Nutrition and the interaction of food nutrients with ethanol metabolism may modulate alcohol toxicity. One such compound is blackcurrant, which also has antioxidant abilities. We investigated the effect of blackcurrant as an antioxidant on the composition and electrical charge of liver cell membranes in ethanol-intoxicated rats. Qualitative and quantitative phospholipid composition and the presence of integral membrane proteins were determined by high-performance liquid chromatography. Electrophoresis was used to determine the surface charge density of the rat liver cell membranes. Ethanol intoxication is characterized by changes in cell metabolism that alter the structure and function of cell membrane components. Ethanol increased phospholipid levels and altered the level of integral proteins as determined by decreased phenylalanine, cysteine, and lysine. Ethanol significantly enhanced changes in the surface charge density of the liver cell membranes. Administration of blackcurrant to rats intoxicated with ethanol significantly protected lipids and proteins against oxidative modifications. It is possible that the beneficial effect of blackcurrant is connected with its abilities to scavenge free radicals and to chelate metal ions.

Acute alcohol intoxication impairs the hematopoietic precursor cell response to pneumococcal pneumonia.

BACKGROUND: Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated. METHODS: Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with S. pneumoniae. Bone marrow, lung, and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S. pneumoniae. RESULTS: Alcohol intoxication impaired the pneumococcal-induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage(-) c-Kit(+) Sca-1(+) (LKS) cell number and colony-forming unit-granulocytes and monocyte (CFU-GM) activity of these cells. Both enhanced proliferation of LKS cells and re-expression of Sca-1 surface protein on downstream progenitor cells bearing lineage(-) c-Kit(+) Sca-1(-) surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these 2 mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection. CONCLUSIONS: Alcohol inhibits the hematopoietic precursor cell response to pneumonia, which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia.

Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum mediated by opioid receptors.

The reinforcing properties of ethanol are in part attributed to interactions between opioid and dopaminergic signaling pathways, but intracellular mediators of such interactions are poorly understood. Here we report that an acute ethanol challenge induces a robust phosphorylation of two key signal transduction kinases, AKT and DARPP-32, in the striatum of mice. Ethanol-induced AKT phosphorylation was blocked by the opioid receptor antagonist naltrexone but unaffected by blockade of dopamine D2 receptors via sulpiride. In contrast, DARPP-32 phosphorylation was abolished by both antagonists. These data suggest that ethanol acts via two distinct but potentially synergistic striatal signaling cascades. One of these is D2-dependent, while the other is not. These findings illustrate that pharmacology of ethanol reward is likely more complex than that for other addictive drugs.

Evaluation of the effects of ethanol on static and dynamic gait.

OBJECTIVE: We used two balance assessment devices, computerized dynamic posturography (CDP) and Swaystar transducers to detect subtle balance system deficits in nine subjects who had ingested minimal amounts of alcohol. DESIGN: Nine subjects were evaluated with both modalities before, and repetitively after, ingesting a small amount of alcohol. METHODS: We measured condition 5 (sway referenced platform; eyes closed) on CDP and tandem walking with eyes closed while wearing Swaystar to see if either test could detect a balance deficit. MAIN OUTCOME MEASURES: We measured total sway amplitude with eyes closed in pitch and roll planes during tandem walking with Swaystar, and static balance scores of CDP sensory organization testing condition 5 before and after alcohol ingestion at 20 min intervals. RESULTS: Although there was no detectable deficit measurable by CDP, eight of our nine subjects showed increased dynamic sway as measured by Swaystar, after alcohol ingestion. Total sway was significantly greater (p=.05) after alcohol ingestion. CONCLUSION: It is important to assess dynamic, rather than static, equilibrium as it may have potential in detecting very subtle balance deficits.

Acute ethanol potentiates the clock-speed enhancing effects of nicotine on timing and temporal memory.

BACKGROUND: Acute ethanol administration potentiates some of the behavioral effects of nicotine, although the extent of this effect is unknown. The present investigation assessed the ability of ethanol to potentiate nicotine's effect on the overestimation of multisecond durations as a result of an increase in the speed of an internal clock. METHODS: Adult male rats were exposed to the acute effects of ethanol (0.0, 0.5, 1.5, and 3.0 g/kg; IG) which was given 10 minutes prior to the administration of nicotine (0.0, 0.3, 0.6, and 1.0 mg/kg; IP). The effects of these combined treatments on timing and temporal memory were assessed using 18- and 36-second peak-interval procedures with separate visual/spatial cues for responding. RESULTS: When administered alone, ethanol had no consistent effect on peak time, but decreased peak rate, and increased peak spread as a function of dose. In contrast, nicotine alone shifted the peak times of the response distributions leftward in a proportional manner as a function of dose. When administered after pretreatment with ethanol, nicotine's effect on the horizontal placement of the peak functions was potentiated. CONCLUSIONS: The observation that ethanol pretreatment potentiates the clock-speed enhancing effects of subsequently administered nicotine is discussed in terms of the role of alpha7-nicotinic acetylcholine receptors and dopamine-glutamate interactions in cortico-striatal circuits thought to subserve interval timing.

Matrix proteolytic activity during wound healing: modulation by acute ethanol exposure.

BACKGROUND: Clinical studies demonstrate that intoxicated patients exhibit an increased incidence of wound healing complications. Previous studies in a murine excisional wound model revealed that acute ethanol exposure impairs the wound healing response, causing decreased angiogenesis and a significant reduction in wound collagen content. METHODS: Using the same murine model of excisional wounding, we examined the effect of a single dose of ethanol on the overall collagen content and collagen type I and type III mRNA expression, transforming growth factor-beta (TGF-beta) production, and levels of several components of the extracellular matrix proteolytic cascade. RESULTS: Wounds from ethanol-treated mice exhibited a significant decrease in collagen and in the production of collagen type I mRNA compared with saline controls. Exposure to ethanol also caused significant increase in wound TGF-beta by day 2 after injury (1.69 +/- 0.29 vs 12.34 +/- 3.97 pg/microg protein, p<0.01). In addition, wounds from mice exposed to ethanol had significantly increased levels of active urokinase plasminogen activator at day 7, (205.10 +/- 48.79 vs 642.70 +/- 159.80 pg/microg protein, p<0.001). The level of matrix metalloproteinase-8, a collagen type I proteinase, was 2.2-fold higher in wounds of ethanol-treated mice compared with control at day 7 (p<0.05). CONCLUSIONS: These studies demonstrate that a single dose of ethanol decreases collagen production, increases the production of TGF-beta and increases levels of matrix degrading enzymes. This alteration in protease balance may partially explain the impaired wound healing that follows acute alcohol intoxication.

Alcohol administration acutely inhibits ghrelin secretion in an experiment involving psychosocial stress.

The appetite-regulating hormones leptin and ghrelin are altered in alcoholism and influence the hypothalamic-pituitary-adrenal system. We investigated whether acute ethanol ingestion and stress exposure affect ghrelin secretion. Nine healthy male volunteers were exposed to a standardized laboratory stressor involving public speaking on 2 days. On the first day they ingested 0.6 g/kg ethanol and on the second a placebo drink 50 minutes before the stressor. Plasma ghrelin, cortisol, glucose, and insulin were measured at baseline and in eight subsequent samples obtained up to 120 minutes after drinking (75 minutes after stress onset). The stress test induced a transient and significant rise in cortisol, which was not altered by prior alcohol administration. No significant change of ghrelin, insulin or glucose levels was observed after the stressor. Ghrelin declined significantly within 15 minutes after alcohol drinking, fell to a minimum of 66% of baseline at 75 minutes and remained at that level until the last sample at 120 minutes. No significant ghrelin changes were observed during placebo experiments. Insulin and glucose were not significantly influenced by stress or by alcohol. We conclude that alcohol drinking acutely attenuates circulating ghrelin levels. This effect is more pronounced than would be expected from the calories ingested with alcohol, as compared with a prior report where liquid meals of different caloric content were administered. We could not observe a stress effect on ghrelin, which does not support a role for ghrelin in stress-induced anorexia.